MicroRNAs (miRNAs) are a class of endogenous, non-coding, single-stranded RNA molecules that are typically 20-25 nucleotides in length. The expression levels of miRNAs in blood, tissue, and other samples are characteristically altered in several disease states. The detection of miRNAs represents a promising avenue for the early diagnosis of various diseases. Consequently, there is a clear need to enhance the sensitivity of miRNA detection to facilitate more accurate disease detection. A fluorescent biosensor was developed that utilizes supramolecular host-guest interactions for assembly and Mo-based materials to initiate a reversible addition-fragmentation chain transfer polymerization (RAFT). The scheme functions by modifying the miRNA on Fe3O4-magnetic nanoparticles (Fe3O4-MNPs), followed by linking the initiator of the subsequent RAFT reaction through supramolecular host-guest interaction. Ultimately, polymerization reactions initiated by Mo compounds result in the formation of polymers with fluorescent monomers on Fe3O4-MNPs. The sensor is extremely sensitive and the detection limit of this sensor is 0.03 fM. Furthermore, the protocol has been demonstrated to be highly effective in the detection of samples in serum, which also serves to illustrate the potential of this fluorescent biosensor for the detection of other kinds of miRNAs.